Polyglycolic acid in solutions

ABSTRACT

HEXAFLUOROISOPROPYL ALCOHOL AND HEXAFLUOROACETONE SESQUIHYDRATE ARE DISCLOSED AS UNIQUE SOLVENTS FOR PREPARING SOLUTIONS OF POLYGLYCOLIC ACID. SUCH SOLUTIONS ARE USEFUL AS SPINNING DOPES FOR WET OR DRY SPINNING OF POLYGLYCOLIC ACID, FOR PREPARING CAST FILMS OF POLYGLYCOLIC ACID, AND FOR PERFORMING A VARIETY OF ANALYTICAL PROCEDURES ON POLYGLYCOLIC ACID WHICH REQUIRE THE POLYMER TO BE IN SOLUTION.

United States Patent US. Cl. 260--32.8 R 2 Claims ABSTRACT OF THEDISCLOSURE Hexafluoroisopropyl alcohol and hexafluoroacetonesesquihydrate are disclosed as unique solvents for preparing solutionsof polyglycolic acid. Such solutions are useful as spinning dopes forwet or dry spinning of polyglycolic acid, for preparing cast films ofpolyglycolic acid, and for performing a variety of analytical procedureson polyglycolic acid which require the polymer to be in solution.

CROSS REFERENCE TO RELATED APPLICATION This application is acontinuation-in-part of our earlier application, Ser. No. 34,593, filedMay 4, 1970 entitled Solutions of Polyglycolic Acid, now abandoned.

BACKGROUND OF THE INVENTION Polyglycolic acid is a known polymer and hasbeen prepared in the past by a variety of processes known to thoseskilled in the art. At least two varieties of this polymer have beendescribed in detail in the prior art. The Higgins, US Pat. 2,676,945,shows the high molecular weight polymers melting at about 232-233 C. andcapable of being fashioned into useful articles and fibers. In the USPat. 3,468,853 polyglycolic acid is shown to be truly polymeric when ithas a crystalline melting point falling between 230 and 232 C. althoughothers have measured this physical property and reported it to fallbetween about 222 C. and 235 C.

Bowman, US. Pat. 3,047,524, on the other hand, describes a class ofoligomeric polymers melting between 90 and 130 C. which are useful inthe field of oxidizer binders for solid propellants.

Oligomers are usually defined as the low members of thepolymeric-homologous series, with molecular weights up to about1000-2000. Homologous oligomers due to their low molecular weight differsufficiently in their physical properties so that they are, in general,far more soluble than their high molecular weight counter-parts. Indeed,we have found this to be true in the case of polyglycolic acid. Highmolecular weight polyglycolic acid is insoluble in all the commonsolvents but linear and cyclic oligomers and high molecular weightheterologs of polyble in a variety of common solvents.

These same solvents are also useful in dissolving the oligomers and highmolecular weight heterologs of polyglycolic acid but not the highmolecular weight polyglycolic acid itself. It seems apparent thereforethat the solubility of high molecular weight polyglycolic acid is asingularly unique phenomenon in the field of polymer science. Forexample, high molecular weight hydroxyacid polymers such as polylacticacid, poly a hydroxy isobutyric acid, polydimethyl ketene, polya,a-diethyl fipropiolactone, poly w-hydroxy caproic acid, and poly 0:-hydroxy decanoic acid are soluble in one or a number of such commonsolvents such as chloroform, benzene, chlorobenzene, toluene, tetralin,anisole, cyclohexane, trifluoro acetic acid and a variety of aromaticand halogenated hydrocarbons. The oligomers and the polymers are alsosoluble in a variety of secondary and tertiary polyhalo alcohols asdescribed by Middleton in U.S. Pat. 3,245,944.

Interest has recently been revived in polyglycolic acid because of thedisclosure of US. Pat. 3,297,033 that the high molecular weight, commonsolvent insoluble, polyglycolic acid has been successfully employed toprepare absorbable surgical sutures. These synthetic sutures provide aviable alternative to the so called catgut sutures which have beenhistorically used by the medical profession when absorbability in livingtissues was required. Several collateral patents relating topolyglycolic acid absorbable sutures have recently appeared, such as,for example, U.S. Pats. 3,457,280, 3,435,008, 3,442,871, 3,442,181,3,468,853, 3,414,939 and 3,463,158 and each of the aforesaid patents areincorporated herein by reference.

Heretofore, the principal way that polyglycolic acid polymer wasfabricated into usable form such as filaments, films, and various othershapes was by the use of melt spinning techniques. Solution techniquescould not be used because they required an acceptable solvent forpolyglycolic acid, and such solvents were not heretofore available. Awide variety of known polymer solvents had been employed in an attemptto solubilize polyglycolic acid but generally to no avail. The lack ofan available acceptable solvent for polyglycolic acid had the effect ofpreventing the use of wet and dry spinning techniques in the fabricationof shaped polyglycolic acid articles. Of the solvents investigated inthe past, several problems have been found to exist. For example, noneof the solvents would dissolve the polyglycolic acid. Moreover, certainother solvents investigated had the effect of chemically degrading thepolymer or otherwise reacting with the polymer in such a way as to breakdown the polymer structure. To briefly summarize, all the commonsolvents heretofore employed had one or more drawbacks which detractedfrom their use as a solvent for polyglycolic acid.

It is therefore an object of this invention to provide unique solventsfor achieving solubility of polyglycolic acid without the attendantdisadvantages of previously employed common solvents.

It is another object of this invention to provide solutions ofpolyglycolic acid which are eminently suitable for the preparation ofvarious shaped forms of polyglycolic acid by various solution techniquessuch as for example, wet and dry spinning.

SUMMARY OF THE INVENTION The invention relates to unique solutions ofpolyglycolic acid. More particularly, it relates to solutions comprisingpolyglyoolic acid dissolved in hexafluoroisopropyl alcohol or inhexafluoroacetone sesquihydrate. The nature of the polyglycolic acidemployed in preparing these solutions, except as indicated hereinbelowwith respect to the degree of crystallinity, is not critical and it hasbeen found, for example, that polyglycolic acid of widely varyingmolecular weight above a minimum of several thousand is quite suitableas is polyglycolic acid prepared from a variety of different processroutes provided that the melting point in the crystalline state fallswithin the range of 222 C. and 235 C.

This invention also relates to various processes which make use of thesolutions of this invention as a means for producing various shapedarticles of polyglycolic acid.

Hexafluoroisopropyl alcohol and hexafiuoroacetone sesquihydrate are bothknown chemicals which are commercially available or can be readilyprepared in accordance with known procedures. For example, see thearticle by Middleton and Lindsey entitled Hydrogen Bonding in FluoroAlcohols in the Journal of the American Chemical Society, vol. 85, pages4948-4952 inclusive. We have found that when either of these two uniquesolvents is employed to dissolve polyglycolic acid, a solui tion ofpolyglycolic acid is readily prepared which re tains solubility of thepolyglycolic acid therein over a wide range of temperatures, and whereinsubstantially no degradation of the polyglycolic acid occurs.

These solutions of polyglycolics acid in either hexafluoroisopropylalcohol or hexafiuoroacetone sesquihy drate are useful as spinning dopesfor wet and dry spin; ning of polyglycolic acid, as a vehicle forpreparing cast films of various thicknesses of polyglycolic acid, andwhen dilute solutions are employed, as a very convenient means forperforming a variety of analytical procedures upon polyglycolic acidwhich require that the polyglycolic acid be in solution.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The solutions and preparationthereof acid used to prepare the solutions is generally of no consequence except for its degree of crystallinity and its melting point inthe crystalline state. However, the nature of the polyglycolic acldemployed does become 1mlytical work a concentration of dissolved polymerof from portant in one respect. If the polyglycolic acid is in asubstantially amorphous form, i.e., less than about 10% .crystallity,the polyglycolic acid will dissolve quickly and completely in bothhexafluoroisopropyl alcohol and in in about 24 hours. More dilutesolutions can of course, be prepared in shorter times and at lowertemperatures. A to solution for example, can be prepared in about 1 to 2hours at 40 C. to 50 C.

In the case of hexafiuoroacetone sesquihydrate solutions of polyglycolicacid, it has been found that solutions containing from about 0.01% toabout 40% poly glycolic acid can be readily prepared. For example, a 40%solution can be prepared at about 65 C. in about 3-6 hours. Again, moredilute solutions can be prepared in shorter times and at lowertemperatures. A 5% to 10% solution, for example, can be prepared inabout 1 to 2 hours at 40 C. to 50 C.

hexafiuoroacetone sesquihydrate. Moreover, it has been generally foundthat if the polyglycolic acid employed possesses a degree ofcrystallinity which is less than about solutions of polyglycolic acid inboth solvents of this invention can still be readily and convenientlyprepared; however, if the degree of crystallinity of the polymer exceedsabout 30%, the polyglycolic acid is soluble only in hexafiuoroacetonesesquihydrate. If the degree of crystallinity exceeds 75%, the polymeris soluble in neither. As the degree or percentage of crystallinity ingcreases, the solubility of the polyglycolic acid diminishes andreciprocally as the degree of crystallinity diminishes, the solubilityof the polyglycolic acid increases. As a consequence, the polyglycolicacid, having a degree of crystallinity between about 0% and 30%, can bedissolved in the hexafluoroisopropyl alcohol in an amount vary-' ingbetween about 0.01% and about 30% by weight of polyglycolic acid basedon the total Weight of solution. On the other hand, if the polyglycolicacid has a degree of crystallinity varying between about 0% and not morethan 75%, the polyglycolic acid can be dissolved in thehexafiuoroacetone sesquihydrate in amounts varying between about 0.01%and about 40% by weight of polyglycolic acid based on the total weightof the solution. The insolubility of crystalline polyglycolic acid inthe cited solvents, however, can be readily overcome by insuring thatthe polyglycolic acid employed to prepare the solutions is in thesubstantially amorphous form. It is a relatively simple procedure toconvert highly crystalline polyglycolic acid into the more desirableamorphous form by simply melting highly crystalline polyglycolic acidand thereupon quenching it quickly to assure formation of the amorphousform of the solid polymer. A typical procedure for convertingcrystalline polyglycolic acid into amorphous polyglycolic acid is shownhereinbelow in Example 5.

The concentration of dissolved polyglycolic acid which exists in thesolutions of this invention can vary over wide ranges. However, the rateof solution of polyglycolic acid in the solvent will increase as thetemperature of the solvent increases. Generally, higher temperatures andlonger contact times can be employed to prepare solutions having highercontents of dissolved polyglycolic acid.

In the case of hexafluoroisopropyl alcohol solutions of polyglycolicacid, it has been found that solutions containing anywhere from about.01% to about 30% by weight polyglycolic acid can be readily prepared.For example, a 30% solution can be prepared at about 65 C.

Analytical utility of solutions Very dilute solutions of polyglycolicacid, i.e., in the range of .01% to 1% by weight, find particularutility as a vehicle for analytically measuring various properties of Asdiscussed heretofore the nature of the polyglycolic the polymer inaccordance with techniques Well known to those skilled in the polymerart; for example, viscosity measurements, and the determination ofmolecular shape and size from light scattering equipment are but a fewof these analytical applications. Generally, for most anaabout 0.1% to0.5% sufiices.

Casting of films onto an appropriate surface which will not stick to theformed film and thereupon providing for removal of the solvent todeposit the film of polyglycolic acid upon the surface. If very thinfilms such as, for. example, membranes or films having thicknesses ofless than about 0.5

a solvent for the hexafluoroisopropyl alcohol or hexafiuoroacetonesesquihydrate wherein the liquid serves as the surface upon which thesolution is deposited and where upon the liquid will extract thehexafluoroisopropyl alcohol or hexafiuoroacetone sesquihydrate leavingdeposited upon the liquid surface a very thin film of polyglycolic acid.Suitable solvents for this purpose include ethyl acetate, tertiary amylalcohol, t-butanol and water.

The concentration of solution employed in preparing cast films will, ofcourse, depend upon the desired thickness of the dried film. Generally,film thicknesses of anywhere from 0.5 mil to about 50 mils, andpreferably 0.5 to 20 mils, can be readily prepared from the solutions ofthis invention- Solutions containing from about 0.5%

to 5% polyglycolic acid are preferred for preparing castfilms inaccordance with the process of this invention.

' The films thus produced are tough, self-supporting films which whenthin are quite clear but which upon standing tend to crystallize andbecome opaque.

Appropriate non-stick surfaces for preparing polyglycolicacid filmsinclude such items as glass, stainless steel, Teflon and variousfiuorinated polymers such as, for example, fluorinated ethylenepropylene copolymers.

Best results are obtained when the casting solution is maintained at atemperature between about room temperature and about 60 C. andpreferably between room" temperature and about 50 C. I

v 5 Wet and dry spinning v The solutions of this invention are eminentlysuitable for spinning into filaments or thin films using the standardtechniques of wet or dry spinning. The term shaped article ofpolyglycolic acid as used herein, means a filament or filaments ofpolyglycolic acid and thin films of or less.

polyglycolic acid, i.e., filrnshaving ath ickness of 10 mils In atypical wet spinning operation, a solution or spinning dope ofpolyglycolic acid dissolved in either hexafluoroisopropyl alcohol orhexa fluoroacetone sesquihydrate is prepared and thereupon extrudedthrough an appropriate extrusion orifice at a solution temperature of 40C. to 80 C., and preferably 60 C. to 80 C., into a suitable liquidcoagulating medium such as, for example, ethyl acetate, tertiary amylalcohol, t-butanol, or water. The coagulating liquid is maintained at atemperature below that of the extrudate, such as, for example, roomtemperature or below, and as low as about 20 C. The coagulant may be anysolvent or system of solvents which coagulates polyglycolic acid andremoves the solvent associated therewith in the spinning solution.

It should be noted that although the boiling point ofhexafluoroisopropyl alcohol is about 58 C. at atmospheric pressure, theboiling point of solutions of polyglycolic acid in hexafluoroisopropylalcohol will exceed 58 C. depending upon how much polymer is dissolvedin the solvent, and the pressure exerted on the system. Thus solutiontemperatures and ranges of temperatures such as 40 to 80 C. and similarranges which appear throughout this specification contemplate thetemperatures of solutions containing varying amounts of polyglycolicacid under varying pressures which can elevate the boiling point of thesolution into the upper limits of such temperature ranges.

A spinning solution will preferably contain as much polyglycolic acid ascan be dissolved in the solution. It has been found in the case ofhexafiuoroisopropyl alcohol that a solution containing from about toabout 30% by weight polyglycolic acid provides an acceptable spinningsolution whereas, when hexafiuoroacetone sesquihydrate is the solvent, apolyglycolic acid concentration of from about 10% to about 40% can beemployed. In general, it is preferred to use as high a concentration ofdissolved polyglycolic acid as possible in the spinning dopes. In thecase of a hexafiuoroisopropyl alcohol spinning dope a polyglycolic acidconcentration of 25-30% is preferred whereas a polyglycolic acidconcentration of 35-40% is preferred when hexafluoroacetonesesquihydrate spinning dopes are used. The spinning dopes may containundissolved polyglycolic acid provided the undissolved particles are ofsufficiently small size so as to not interfere with the extrusion of thesolutions.

As the extrudate contacts the coagulant bath, it coagulates to form ashaped article of polyglycolic acid which is then washed with a solventsuch as water, ethyl acetate, or tertiary amyl alcohol to removeresidual hex afiuoroacetone sesquihydrate or hexafluoroisopropylalcohol. The shaped article is then stretched in accordance withstandard fiber or film making procedures to orient the polyglycolicacid. In the case of a filament of polyglycolic acid, the strand willtypically be stretched anywhere from three to seven times its originallength. In the case where the shaped article is a thin film ofpolyglycolic acid, it may be similarly stretched or it may be subjectedto a biaxial stretch or from about three to seven times its originallength in the longitudinal direction and from about two to five timesits original length in the lateral direction. The shaped article can bestretched before or after removal of residual solvent or concurrentlywith the removal of the solvent.

The solutions of this invention are also eminently suitable for thepreparation of shaped articles of polyglycolic acid using dry spinningtechniques. The solution concentrations which have been found suitableare the same as those discussed hereinabove for Wet spinning. Thetemperatures at which the solutions are extruded are also the same asthose discussed hereinabove for wet spinning. The extrudate emerges intoa suitable gaseous inert medium which is usually a hot stream of astripping gas such as, for example, air, nitrogen, or argon, which ismaintained at a sufficiently high temperature to evaporate, from thespinning solution, the solvent associated therein with the polyglycolicacid. The temperature of the EXAMPLE 1 Preparation of polyglycolic acidsolutions A variety of solutions of polyglycolic acid in bothhexafluoroisopropyl alcohol and hexafiuoroacetone sesquihydrate ofvarious concentrations were prepared by admixing solvent and solute inthe required portions and agitating the mixture at a prescribedtemperature until solubility was achieved. The data shown below areillustrative of the polyglycolic acid solutions prepared.

Percent Temp.

Solvent by wt. 0.) Hours Hexafluoroisopropyl alcohoL.-- 19 55 3Hexafluoroacetone sesquihydra 19 55 2 Hexafluoroisopropyl alcohol 26 5516 Hexnfiuoroacetone sesquihydrate 26 55 2 Hexafluoroisopropyl alcohol30 65 24 Hexafluoroacetone sesquihydrate- 35 65 3 1 Dissolved polglycolic acid. a Time require to achieve complete solution.

EXAMPLE 2 Dry spinning of polyglycolic acid A spinning solution wasprepared by dissolving 30 parts by weight of polyglycolic acid having anintrinsic viscosity of 1.2 in 70 parts by weight of hexafluoroisopropylalcohol at 55 C. The solution was heated to 70 C. and pumped at the rateof 30 cc. per minute through a spinnerette having 16 capillaries micronsin diameter into a vertical column 20 cms. in diameter and 6 meterslong. The upper portion of the column was maintained at C. for a lengthof 4 /2 meters. The lower 150' cms. of the column was flushed withnitrogen at ambient temperature. A finish consisting of 10% mineral oilin xylene was applied and the yarn taken up at 300 meters/min. The yarnwas found to contain 32.6% solvent which was removed in a vacuum oven at35 C. overnight. The solvent-free yarn had a denier of 270.

This yarn was stretched in turbulent hot air at 80 C. to 3.5 to 5.5times its original length, and heat-set at C. for two hours to improvestrength retention in living tissue when the yarn is used in the form ofa braided surgical suture.

Similar results were obtained when the hexafluoroisopropyl alcohol wasreplaced with hexafluoroacetone sesquihydrate.

EXAMPLE 3 Wet-spinning of polyglycolic acid 30 parts by weight ofpolyglycolic acid were dissolved in 70 parts by weight ofhexafiuoroisopropyl alcohol at 50 C. The resulting spin dope was pumpedat a rate of 27 cc./min. through a heater which warmed it to atemperature of 60 C., and then through a 20-hole spinnerette with 100micron capillary diameters which was submerged in an ambient temperaturewater bath 2 meters in length. The coagulated wet gel was pulled away ata speed of 30 meters per minute and subjected to a countercurrent washwith tap water using 30' wraps on a pair of advancing rolls, the ends ofwhich were elevated 20 above horizontal.

The washed gel was then led through a 60 C. waterbath and stretched toabout 7 times its original length.

Free water was removed by sponges and aspirators as the stretched gelleft the Water bath. The gel was further dried, and stretched 3-fold, bydrawing in 150 C. air to achieve a final denier of 195.

Similar results were obtained when the hexafluoroisopropyl alcohol wasreplaced with hexafluoroacetone sesquihydrate.

EXAMPLE 4 Casting of polyglycolic acid film A solution of 25%polyglycolic acid (by weight)in hexafluoroacetone sesquihydrate wasprepared by heating the mixture to 50 C. with stirring. The solution waspoured onto a clean, smooth glass plate using a draw down blade todistribute the solution over the glass to a depth of about 5 microns.The solvent was allowed to evaporate and the resulting polyglycolic acidfilm was removed by peeling it off the glass.

The film produced was a tough, self-supporting clear film ofpolyglycolic acid. Similar results were obtained when hexafluoroacetonesesquihydrate was replaced with hexafiuoroisopropyl alcohol.

Conversion of crystalline polyglycolic acid to A amorphous polyglycolicacid Fivegrams of polyglycolic acid which had been annealed at 175 C.for 24 hours was found to be insoluble in hexafiuoroisopropyl alcoholeven when heated to 60 C. This sample of polyglycolic possessed a degreeof crystallinity greater than 40%. It was placed in a melt index unit,heated to 245 C. and extruded through a 30 mil orifice into liquidnitrogen by applying 20,000 p'.s.i. to the piston of the unit. Thesubstantially amorphous noodle was removed-from the liquidnitrogen andallowed to warm up to room temperature in a vacuum dessicator. Thistreated polyglycolic acid was now readily soluble in ml. ofhexafiuoroisopropyl alcohol at roomtemperature. I I

We claim:

1. A solution comprising polyglycolic acid-having'a crystalline meltingpoint between about 222 C. and 235 C. and having a degree ofcrystallinity not greater than about 30% dissolved inhexafluoroisopropyl alcohol in an amount varying between 0.01% and 30%by Weight of polyglycolic acid based on the total weight of thesolution. "1

2. A solution comprising polyglycolic acid having a crystalline meltingpoint between about 222 C. and 235 C. and having a degree ofcrystallinity not exceeding about dissolved in hexafluoroacetonesesquihydrate in an amount varying between about 0.01% and 40% by weightof said polyglycolic acid based on the total weight of the solution.

References Cited UNITED STATES PATENTS

